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Acute Porphyrias

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Acute porphyrias are hereditary disorders of haem biosynthesis; they have a prevalence of about 1 in 75 000 of the population. BNF states that if no safe alternative, drug treatment for serious or life-threatening conditions should not be withheld from patients with acute porphyria.

About

Disruption of Heme synthetic pathway
Build up of precursors causes toxicity
Great care must be taken when Prescribing

National UK Links

Causes

Type of Porphyria	Details
Acute Intermittent Porphyria (AIP)	The most common acute porphyria, caused by a deficiency in the enzyme porphobilinogen deaminase (PBGD). It typically presents with abdominal pain, neuropsychiatric symptoms, and autonomic dysfunction.
Hereditary Coproporphyria (HCP)	Caused by a deficiency in coproporphyrinogen oxidase, leading to an accumulation of coproporphyrins. Symptoms are similar to AIP but may also include skin sensitivity to sunlight.
Variegate Porphyria (VP)	Caused by a deficiency in protoporphyrinogen oxidase. It presents with both acute neurovisceral attacks and photosensitivity, leading to blistering of the skin upon exposure to sunlight.
ALAD Deficiency Porphyria (ADP)	A rare type of porphyria caused by a deficiency in delta-aminolevulinic acid dehydratase (ALAD). It primarily presents with neurovisceral symptoms during acute attacks.

Precipitant

Genetic mutations leading to enzyme deficiencies in the heme biosynthesis pathway.
Precipitating factors include drugs (e.g., barbiturates, sulfonamides), alcohol, fasting, and hormonal changes (e.g., menstruation).
Environmental factors like infections or stress can also trigger an acute attack.

Drugs to avoid - See BNF for more

Anabolic steroids
Antidepressants, MAOIs (contact UKPMIS for advice)
Antidepressants, Tricyclic and related (contact UKPMIS for advice)
Barbiturates (includes primidone and thiopental)
Contraceptives, hormonal (contact UKPMIS or a porphyria specialist)
Hormone replacement therapy (for detailed advice contact UKPMIS or a porphyria specialist)
Imidazole antifungals (PO/IV use; topical antifungals safe due to low systemic exposure)
Non-nucleoside reverse transcriptase inhibitors (contact UKPMIS for advice)
Progestogens (for detailed advice contact UKPMIS or a porphyria specialist)
Protease inhibitors (contact UKPMIS for advice)
Sulfonamides (includes co-trimoxazole and sulfasalazine)
Sulfonylureas (glipizide and glimepiride are thought to be safe)
Taxanes (contact UKPMIS for advice)
Triazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)

Clinical

Abdominal Pain and Neurological symptoms
Muscle weakness which can involve respiratory muscles
Delirium, progressive paralysis, Tetraplegia
Psychosis, hallucinations, Constipation, fatigue, irritable
Can last hours days even weeks
Tachycardia is often an indicator of disease state progression.
VP/HCP can have bullous eruptions on sun exposed areas
Abdominal exam does not match the pain severity.
Urine is dark and can be Red brown urine.

Investigations

Diagnostic Test	Details
Urine Test for Porphobilinogen (PBG)	The most important initial test during an acute attack. Elevated levels of PBG in urine are indicative of acute porphyrias, particularly Acute Intermittent Porphyria (AIP).
Urine Test for Delta-Aminolevulinic Acid (ALA)	Elevated levels of ALA in the urine are also common during an acute attack and support the diagnosis of acute porphyrias.
Plasma or Serum Fluorescence	Plasma or serum shows a characteristic fluorescence under ultraviolet light in cases of Variegate Porphyria (VP) and Hereditary Coproporphyria (HCP).
Stool Analysis for Porphyrins	Useful in diagnosing Variegate Porphyria (VP) and Hereditary Coproporphyria (HCP), as these porphyrias cause elevated levels of porphyrins in stool samples.
Genetic Testing	Confirms the specific type of porphyria by identifying mutations in the genes responsible for the enzyme deficiencies in the heme biosynthesis pathway.
Liver Function Tests (LFTs)	While not diagnostic of porphyria itself, LFTs can help assess liver involvement and monitor potential hepatic complications in porphyria patients.
Measurement of Enzyme Activity	Measuring the activity of specific enzymes (e.g., PBG deaminase) can help diagnose certain types of porphyrias, such as AIP.

BNF: Haem arginate is administered by short intravenous infusion as haem replacement in moderate, severe, or unremitting acute porphyria crises. In the United Kingdom the National Acute Porphyria Service (NAPS) provides clinical support and treatment with haem arginate from two centres (Cardiff and Vale University Health Board and King's College Hospital) (see Useful resources).

Drugs to avoid (check all): Diclofenac, Alcohol, OCP, HRT, TCA, Benzodiazepines, Anaesthetic agents (barbiturates, halothane), Antibiotics (cephalosporins, sulfonamides, macrolides, tetracyclines, rifampicin, trimethoprim, chloramphenicol, metronidazole), Metoclopramide, ACEI, CCB, Statins, Anticonvulsants, Furosemide, Sulfonylureas, Lidocaine, Gold salts, Antihistamines, Amphetamine

Management: In the UK contact National Acute Porphyria Service (NAPS)

EmergencyABC, Close monitoring. Dark quiet room.
Immediate Management: Cessation of precipitating factors (e.g., withdrawal of offending drugs).
IV Dextrose/Glucose: Administration to inhibit hepatic heme synthesis.
Hemin Infusion: To replenish the deficient heme and reduce porphyrin precursor production.
Symptomatic Treatment: opioids, anti-emetics for nausea, and beta-blockers for autonomic symptoms.
Long-term Management: Avoidance triggers, monitoring for liver function and neurological status.

Prevention

Avoid heavy alcohol, starvation, causative drugs
VP/HCP avoid sun exposure or wear sun blocks
Risk of hepatocellular carcinoma so needs surveillance

References

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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